LEC

Inbr. F50 (Hok).

Colour: Cinamon-like.

Genet. ?

Origin: Misima, Japan 1956 from a cross between a wild rat and "Castle's black rat". To Hok in 1975 at F32 (Sasaki, personal communication).

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Characteristics

Carries a mutation causing fulminant hepatitis and jaundice at about four months of age. Clinical symptoms include severe jaundice, bleeding, oliguria, loss of body weight and elevation of serum levels of bilirubin and hepatic enzymes. About half the animals die within a week of onset, and in survivors hepatocellular carcinoma spontaneously appears after 1-1.5 years (Kasai et al 1990, Sasaki 1985, Wirth et al 1990). The characteristics of the strain have been reviewed by Mori et al, (1994).

Liver cytochrome P450 levels were substantially reduced both at 4 weeks and at 3 month of age, but epoxide hydrolase, gamma-glutamyltranspeptidase and UDP-glucuronyl-transferase activities were significantly elevated at four weeks (Sugiyama et al 1988). Liver gangliosides are abnormal (Kasi et al 1993). There is a gross accumulation of copper in the liver which is associated with the hepatitis. Copper levels can be reduced by treatment with D-penicillamine (Togashi et al, 1992). Highly sensitive to whole body irridation when compared with WKAH (Hayashi et al, 1992, 1993). It appears to be an animal model of Wilson's disease in humans (Yamada et al, 1993). There are abnormalities in ethanol and acetaldehyde metabolizing enzymes (Nakajima et al, 1993).

Other papers describing the LEC strain include Miyoshi et al, (1993a, b), Kato et al (1993), Yamamoto et al, (1993), Suzuki et al, (1993, 1994, 1995), Ito et al, (1994), Sakurai et al, (1994), Kanno et al, (1994a,b), Sakai et al, (1994), Ikeda et al, (1994), Okui et al, (1994), Suzuki and Kuroda (1994), Muramatsu et al, (1995), Yamada et al, (195), Ohhira et al, (1995)

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Hayashi M., Endoh D., Kon Y., Yamashita T., Hashimoto N., Sato F., Kasai N., and Namioka S. (1992) Higher sensitivity of LEC strain rat in radiation-induced acute intestinal death. J. Vet. Med. Sci. 54, 269-273.

Ikeda Y., Sugiyama T., Takahashi M., and Taniguchi N. (1994) Selective suppression of Igg2a subclass in LEC rats during development. Biochimica Et Biophysica Acta-General Subjects 1200, 277-280.

Ito Y., Fujie K., Matsuda S., Takahashi R., and Maeda S. (1994) Long-Evans-A and Long-Evans-C rat strains susceptible to clastogenic effects of chemicals in the bone-marrow cells. Jpn. J. Cancer Res. 85, 26-31.

Kasai T., Osaai T., Miyoshi I., Kamimura E., Yoshida M. C., and Dempo K. (1990) Clinico-pathological studies of LEC rats with hereditary hepatitis and hepatoma in the acute phase of hepatitis. Lab. Animal Sci. 40, 502-505.

Kato J., Kohgo Y., Sugawara N., Katsuki S., Shintani N., Fujikawa K., Miyazaki E., Kobune M., Takeichi N., and Niitsu Y. (1993) Abnormal hepatic iron accumulation in LEC rats. Jpn. J. Cancer Res. 84, 219-222.

Mori M., Hattori A., Sawaki M., Tsuzuki N., Sawada N., Oyamada M., Sugawara N., and Enomoto K. (1994) The LEC rat - a model for human hepatitis, liver-cancer, and much more. Am. J. Pathol. 144, 200-204.

Muramatsu Y., Agui T., Sakai T., Yamada T., and Matsumoto K. (1995) The diversity of T-cell receptor repertoire of peripheral CD4(+) lymphocytes in LEC mutant rats. Immunology Letters 45, 173-177.

Nakajima M., Kato J., Kohgo Y., Katsuki S., Inui N., Ohya M., Takeichi N., and Niitu Y. (1993) Abnormal ethanol-metabolism in Long-Evans Cinnamon rats, a mutant strain developing spontaneous hepatoma. Alcohol and Alcoholism 28, 105-108.

Ohhira M., Ono M., Ohhira M., Sekiya C., Namiki M., Fujimoto Y., Naga M., and Mori M. (1995) Changes in free radical-metabolizing enzymes and lipid peroxides in the liver of Long-Evans with Cinnamon-like coat color rats. Journal of Gastroenterology 30, 619-623.

Okui T., Hayashi M., Endoh D., Sato F., Kasai N., Watanabe T., and Namioka S. (1994) A high-frequency of induction of chromosome-aberrations in the bone- marrow cells of LEC strain rats by X-irradiation. Mutation Research Letters 324, 165-169.

Sakai T., Agui T., and Matsumoto K. (1994) Intestinal intraepithelial lymphocytes in LEC mutant rats. Immunology Letters 41, 185-189.

Sakurai H., Satoh H., Hatanaka A., Sawada T., Kawano K., Hagino T., and Nakajima K. (1994) Unusual generation of hydroxyl radicals in hepatic copper- metallothionein of LEC (Long-Evans Cinnamon) rats in the presence of hydrogen-peroxide. Biochemical and Biophysical Research Communications 199, 313-318.

Sasaki M. (1985) Spontaneous hepatitis in an inbred strain of Long Evans rats. Rat News Lett. 14, 4-6.

Sugiyama T., Takeichi N., Kobayashi H., Yoshida M. C., Sasaki M., and Taniguchi N. (1988) Metabolic predisposition of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma: alterations of the drug metabolizing enzymes. Carcinogenesis 9, 1569-1572.

Suzuki K. T. and Kuroda T. (1994) Direct transfer of copper from metallothionein to superoxide- dismutase - a possible mechanism for differential supply of Cu to SOD and ceruloplasmin in LEC rats. Research Communications in Molecular Pathology and Pharmacology 86, 15-23.

Togashi Y., Li Y., Kang J. H., Takeichi N., Fujioka Y., Nagashima K., and Kobayashi H. (1992) D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper-metabolism. Hepatology 15, 82-87.

Wirth P. J., Fujimoto Y., Takahashi H., Mori M., Yoshida M. C., Sugimura T., and Nagao M. (1990) Two-dimensional electrophoretic analysis of hepatitis-associated polypeptides in liver of LEC rats developing spontaneous hepatitis. Jpn. J. Cancer Res. 81, 477-482.

Yamada T., Moralejo D., Agui T., and Matsumoto K. (1993) Biochemical polymorphisms in Long-Evans Cinnamon (LEC) inbred strain of rat. J. Vet. Med. Sci. 55, 491-492.

Yamamoto F., Kasai H., Togashi Y., Takeichi N., Hori T., and Nishimura S. (1993) Elevated level of 8-hydroxydeoxyguanosine in DNA of liver, kidneys, and brain of Long-Evans Cinnamon rats. Jpn. J. Cancer Res. 84, 508-511.

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INBRED STRAINS OF RATS
Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK